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Background Data on the efficacy and tolerability of latent tuberculosis infection (LTBI) treatment in cancer patients receiving checkpoint inhibitor immunotherapy (CPI) is limited. We sought to assess LTBI therapy and its adverse events and outcomes in patients treated with CPI. Methods We performed a retrospective cohort study at MD Anderson Cancer Center of adult patients, between April 2016 and May 2021, who were receiving CPI and were diagnosed with LTBI based on positive T-SPOT TB test. We then compared those patients treated with isoniazid (INH) 5mg/kg daily versus those that did not receive INH therapy. Results We identified 35 patients treated with CPI who had a diagnosis of LTBI. Patients were divided into 2 groups: CPI alone (23 patients, 65.7%) and CPI+INH (12 patients, 34.3%). The majority of patients in both groups had renal cell carcinoma (34.3%) and melanoma (17.1%). Nivolumab as monotherapy was the most commonly used CPI agent in both groups (37.1%), whereas nivolumab and ipilimumab combination was mainly used in the CPI group (34.7%) compared to CPI+INH group (8.3%). In the CPI+INH group, 7 patients (58.3%) developed moderate to severe hepatoxicity that led to discontinuation of INH and CPI therapy versus none in the CPI group (p= 0.001). There was no statistically significant difference in the alanine aminotransferase (ALT) at baseline between both groups (p=0.117), whereas the median ALT level was significantly higher during CPI+INH therapy compared to CPI alone (135 U/L vs 24 U/L respectively, p=0.025. Furthermore, immune-related adverse events were reported in a total of 12 of 35 patients (34.2%). None of the patients in either group developed tuberculosis reactivation during a follow up period of up to 1148 days. Conclusion Our data suggest that latent tuberculosis reactivation is rare in cancer patients on CPI immunotherapy. Hepatotoxicity remains a concern in this patient population with LTBI treated with CPI and INH. With the widespread use of CPI, close laboratory and clinical monitoring is required to avoid life-threatening drug-induced liver injury and interruption of LTBI therapy and immunotherapy. Further clinical studies are warranted to determine the optimal management of LTBI during CPI therapy. Disclosures Pablo C. Okhuysen, MD, FACP, FIDSA, Deinove Pharmaceuticals (Grant/Research Support)Ferring Pharmaceuticals (Consultant)Melinta Therapeutics (Grant/Research Support)Merck & Co. (Grant/Research Support)Napo Pharmaceuticals (Consultant, Scientific Research Study Investigator, Research Grant or Support)Singulex (Consultant)Summit Therapeutics (Grant/Research Support) Dimitrios P. Kontoyiannis, MD, Astellas (Consultant)Cidara Therapeutics (Advisor or Review Panel member)Gilead Sciences (Consultant, Grant/Research Support, Other Financial or Material Support, Honoraria)

Background The prevalence of chronic hepatitis C virus (HCV) infection in patients with cancer in the U.S. has been reported to be 1.5% overall and up to 10.6% in specific subgroups. Testing for antibody to HCV (anti-HCV) is a low-cost diagnostic method in widespread use worldwide; however, the optimal screening test for HCV in cancer patients has not been established. We sought to identify the optimal screening test for HCV in patients with hematologic malignancies and/or prior hematopoietic cell transplant (HCT). Methods New patients who were seen at the Lymphoma/Myeloma, Leukemia, and Stem Cell Transplant clinics at MD Anderson Cancer Center (02/11/2019-11/5/2019) were simultaneously screened for HCV with serologic (antibody to HCV [anti-HCV]) and molecular (HCV RNA) assays. Anti-HCV testing was performed by using the ARCHITECT Anti-HCV assay and HCV RNA testing was performed by using the Cobas HCV test. The agreement between the two tests was evaluated using Cohen’s kappa statistic and McNemar’s test. All tests were two-sided with a significance level of 0.05. Results A total of 214 patients were enrolled in the study, of whom 127 (59%) were men (Table), One hundred forty-nine patients (70%) had a lymphoid neoplasm, 65 (30%) had a myeloid neoplasm, and 15 (7%) underwent HCT. Ninety-three patients (43%) had progressive disease. Three patients (1.4%) had positive anti-HCV, and two (0.9%) had positive HCV RNA. The overall percentage agreement was 99.5% (95% CI, 97.4% to 99.9%). Of the 3 patients with positive anti-HCV, 2 had positive and 1 had negative HCV RNA. There were no cases of seronegative HCV infection. The positive percentage agreement was 66.7% (95 CI, 20.8% to 93.9%), and the negative percentage agreement was 100.0% (95% CI, 98.2% to 100.0%). Cohen’s Kappa coefficient was 0·80 (95% CI, 0.41 to 1.00, p < 0·0001), indicating substantial agreement between anti-HCV and HCV RNA tests for diagnosis of HCV infection. Conclusion The diagnostic yield for screening for chronic HCV infection in heavily immunocompromised cancer patients is similar for serologic and molecular testing. The use of anti-HCV, a diagnostic method with low cost, in patients with cancer would contribute to the World Health Organization’s goal of HCV elimination worldwide. Table. Characteristics of the study population (n=214) Disclosures Harrys A. Torres, MD, Merck & Co., Inc. (Grant/Research Support) Issam I. Raad, MD, Citius (Other Financial or Material Support, Ownership interest)Cook Medical (Grant/Research Support)Inventive Protocol (Other Financial or Material Support, Ownership interest)Novel Anti-Infective Technologies (Shareholder, Other Financial or Material Support, Ownership interest)

Background Several cases of severe bacterial, fungal, and viral infections have been reported following ibrutinib therapy. Here, we report a case of a patient with non-Hodgkin lymphoma who developed hepatitis B virus (HBV)–associated liver failure after anti-cancer treatment most recently with ibrutinib. We also review reported cases of HBV reactivation (HBVr) after ibrutinib. Methods We searched the Medline and Embase databases and identified 5 patients with HBVr related to ibrutinib for a total of 6 study patients, including our case (figure). HBV-related outcomes were defined according to the 2018 AASLD HBV guidance document. Results All 6 patients were men and most (5 or 83%) had chronic lymphocytic leukemia and past HBV infection (table). Three patients (50%) developed HBV-related hepatitis and 2 of them progressed to liver failure. Four patients (67%) had a remote history (≥24 months) of other potential risk factors besides ibrutinib that could contribute to HBVr, including the use of direct-acting antivirals for hepatitis C co-infection (1 pt), hematopoietic cell transplant (HCT) (1 pt) and rituximab use (4 patients). HBVr occurred at least 6 months after initiation of ibrutinib in most patients (4 or 67%), with a median of 9.7 months (range, 1.5–42). In all 4 patients pretreated with rituximab, that treatment was completed at least 24 months before HBVr. Two of these patients received anti-HBV prophylaxis that was stopped 12 months after the completion of rituximab; the other 2 patients were only monitored without antivirals. The HCT recipient received anti-HBV prophylaxis per guidelines. None of the 6 patients treated with ibrutinib were receiving anti-HBV prophylaxis at the time of HBVr, but 5 patients were started on anti-HBV drugs at the first sign of HBVr. Four received entecavir and 1, tenofovir. All treated patients recovered from HBVr. No pt died of HBVr. Conclusion Life-threatening HBVr can occur following ibrutinib therapy in patients with past or chronic HBV infection. The temporal association between ibrutinib therapy and reactivation indicates that ibrutinib is the likely cause of the HBVr, and clinicians should be aware of the risk of HBVr in these patients. A provisional approach could be HBV monitoring at regular intervals with initiation of antiviral therapy at the earliest sign of HBV reactivation. Disclosures All authors: No reported disclosures.

Background Short-duration with an 8-week course of ledipasvir/sofosbuvir (LDV/SOF) or glecaprevir/pibrentasvir (GLE/PIB) is considered adequate to treat hepatitis C virus (HCV) infection in selected patients. However, immunocompromised patients with HCV/HIV are not eligible for this approach. Herein, we study the efficacy and safety of an 8-week therapy with direct-acting antivirals (DAAs) in HCV-infected cancer patients. Methods HCV-infected patients with any type of cancer followed at MD Anderson Cancer Center (June 2014–April 2018) and treated with an 8-week course of LDV/SOF or GLE/PIB were enrolled in a prospective observational study. Efficacy was calculated based on achieving sustained virologic response at 12 weeks (SVR12) after end of treatment per intention to treat (ITT) analysis. A posthoc per-protocol (PP) analysis was done in patients with 12 weeks of follow-up post DAAs. Safety was assessed by emergence of adverse events (AEs) and clinically significant drug–drug interactions (DDIs). Results Twenty-four patients were treated with a short-duration of DAAs, 22 with LDV/SOF and two with GLE/PIB. General characteristics are described in Table 1. Five patients received concomitant cancer treatment (nivolumab, sorafenib, lenalidomide, tamoxifen and leuprolide), without DDIs noted. Among the patients who have completed DAAs, SVR rates were 87% per ITT (20/23) and 100% PP (20/20) analyses. No patients had grade 2, 3 or 4 AEs. Conclusion This is the first prospective study to evaluate the use of short-duration of DAAs in HCV-infected cancer patients where these regimens were found to be effective and safe. Table 1. General Characteristics Characteristics Patients N (%) Number of patients 24 Age, median (interquartile range) 61 (57–66) Male sex 18 (75) Black race 9 (38) Obesity (body mass index >30) 10 (42) HCV genotype 1a 17 (71) 1b 5 (21) 2 2 (8) Type of cancer Hematologica 6 (25) Solidb 18 (75) a Multiple myeloma (2), acute myeloid leukemia (2), non-Hodgkin lymphoma (2). b Prostate (3), head and neck (3), lung (3), renal (2), anal (2), ovarian (2), breast (1), thyroid (1), gastrointestinal stromal tumor (1). Disclosures H. Torres, Gilead Sciences, Merck & Co., Inc.: Grant Investigator, Grant recipient. Vertex Pharmaceuticals: Grant Investigator, Grant recipient.

Background Reactivation of hepatitis B virus (HBV) can occur in patients after cancer therapies. Direct-acting antivirals (DAAs) are the effective therapies for hepatitis C virus (HCV) infection, and HBV reactivation in HCV/HBV co-infected patients treated with DAAs has been reported. We analyzed the risk of HBV reactivation among HCV/HBV co-infected cancer patients being treated with DAAs. Methods We prospectively followed patients with any type of cancer and HCV treated with DAAs between January 2014 and January 2018 at MD Anderson Cancer Center. Information on demographics, use of radiation, chemotherapy, immunotherapy, or anti-CD20 antibodies, and anti-HBV therapy were collected. All patients had the following tests at baseline, 2 and 4 weeks after initiation of DAAs, at end of treatment (EOT), and 12 weeks after completion of DAAs: alanine aminotransferase, total bilirubin, HBV surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), and HBV DNA and HCV RNA levels. We defined the following outcomes by AASLD-recommended parameters: HBV reactivation (HBsAg reverse seroconversion, HBV DNA >2 log compared with baseline, HBV DNA >3 log if HBV DNA was undetectable, or >4 log if baseline was unavailable), hepatitis flare (ALT increase ≥3 times baseline and >100 U/L), and HBV-associated hepatitis (HBV reactivation and hepatitis flare). Patients were followed for 12 weeks after completion of DAAs. Results Of 169 cancer patients treated for HCV infection, 2.4% (n = 4) had chronic HBV infection (HBsAg+/anti-HBc+), and most (3/4) of these were on anti-HBV therapy. Past HBV infection (HBsAg-/HBcAb+) was noted in 30% (51/166), and none received anti-HBV therapy. Of these, 37% (19/51) had cancer therapy within 6 months prior to DAA treatment. HBV reactivation did not occur in any co-infected patients. Two patients had hepatitis flare, but none developed HBV-associated hepatitis. Conclusion This is the first prospective study evaluating HBV reactivation in HCV/HBV co-infected cancer patients receiving DAAs. The risk of HBV reactivation in these patients seems to be low. Future studies with a larger cohort of co-infected cancer patients allowing personalized risk stratification are needed. Disclosures J. P. Hwang, Gilead Sciences: Investigator, Grant recipient; Merck & Co., Inc.: Investigator, Grant recipient. H. Torres, Gilead Sciences, Merck & Co., Inc.: Grant Investigator, Grant recipient; Vertex Pharmaceuticals: Grant Investigator, Grant recipient.

Background Hepatitis C virus (HCV)-infected patients with hepatocellular carcinoma (HCC) are at high risk for direct-acting antiviral (DAA) failure and controversy exists on the increased risk of HCC recurrence following DAAs. Herein, we evaluate the efficacy, safety and oncologic outcomes of HCV-infected patients with HCC treated with DAAs. Methods This prospective observational study included consecutive patients seen at MD Anderson Cancer Center (January 2014–April 2017). Patients received 1 out of 5 different combinations. Efficacy was assessed by intention-to-treat (ITT) analysis based on sustained virological response 12 weeks after finishing DAAs (SVR12). Adverse events (AEs) and clinically significant drug-drug interactions (DDIs) were analyzed. AEs were graded according to the Division of AIDS Table (v 2.0). Cancer response was evaluated at the time of initiation and 6 months after finishing DAAs. Results Twenty-seven patients were enrolled. The majority were men (85%), white (55%) with genotype 1 HCV (66%), Child-Pugh score A (85%), tumor stage 4 (41%) and eligible for potentially curative options (74%). The SVR12 (ITT) data are depicted in table. The most common AEs were headache (11%) and anemia (7%). Only one pt had grade 3 AE (renal failure) but grade 4 AEs or DDIs were not observed. Among patients with potentially curable HCC (n = 20), the disease control rate was 35% (complete remission 10%, partial remission 25%) with recurrence rate of 5% (1 pt). None of the patients had de novo HCC within 6 months of DAAs. All 7 patients with unresectable HCC had stable disease within 6 months of DAAs. Conclusion DAAs appear to be safe but of suboptimal efficacy in HCV-infected patients with HCC. More studies are needed to identify the subset of patients who will benefit from DAAs. Table. SVR12 rates Variable SVR12 (ITT) Overall 18 (66) Treatment regimen Sofosbuvir+ Ribavirin 2/3 (66) Sofosbuvir+ Simeprevir 2/3 (66) Ledipasvir/Sofosbuvir 10/16 (63) Sofosbuvir/Velpatasvir 3/4 (75) Paritaprevir/Ritonavir/Ombitasvir/Dasabuvir 1/1 (100) Genotype 1 12/18 (66) 1a 10/15 (66) 1b 1/2 (50) 2 3/4 (75) 3 0/2 (0) Othera 3/3 (100) Type of HCC Potentially curable 14/20 (70) Unresectable 4/7 (57) aOther genotypes included genotype 6 (1) and mixed genotypes (2). Disclosures H. Torres, Gilead Sciences: Consultant and Grant Investigator, Consulting fee, Grant recipient and Research support. Merck & Co: Consultant and Grant Investigator, Consulting fee and Grant recipient. Janssen Pharmaceuticals, Inc.: Consultant, Consulting fee. Dynavax Technologies: Consultant, Consulting fee

Background Hepatitis C virus (HCV) infection is associated with the development of B-cell Non-Hodgkin lymphoma (NHL). Several studies report regression of indolent NHL in HCV-infected patients treated with interferon (IFN)-containing therapy without chemotherapy. We are describing, herein, the oncologic response of patients with such cancers treated with only direct antiviral agents (DAAs). Methods Patients with HCV-associated NHL seen at MD Anderson Cancer Center (6/2014 to 6/2017) and treated with DAAs were followed and those with indolent NHL treated with DAAs were further analyzed. DAA regimens were administered according to guidelines for HCV-infected patients without cancer. Efficacy was calculated on the basis of achieving sustained virologic response 12 weeks (SVR12) after end of treatment (EOT). NHL status was evaluated at the time of DAAs initiation and response was prospectively analyzed at 6 months after EOT using WHO criteria. Results Six patients received DAAs alone as first-line management of their NHL. Most patients 5/6 (83%) did respond to such treatment avoiding or delaying the use of chemotherapy (Table). Conclusion As described with IFN-containing therapy, the oncologic outcome of HCV-infected patients with indolent NHL could also improve by using only DAAs. Table: Characteristics of six patients with indolent NHL treated with DAAs. Number of patients (%) N = 6 Median age (IQR), years 60 (55- 65) Gender, male 4 (67) NHL subtype Marginal zone lymphomaa 6 (100) HCV genotype 1 3 (50) 2 3 (50) rs12979860 genotypeb CC 2 (33) CT 3 (50) TT 1 (17) Cirrhosis 0 History of HCV treatment 0 DAA therapy Sofosbuvir + ribavirin 2 (33) Sofosbuvir + simeprevir 1 (17) Sofosbuvir + daclatasvir 2 (33) Sofosbuvir + ledipasvir 1 (17) DAA treatment duration of 12 weeks 6 (100) NHL response after SVR Complete response 2 (33) Partial response 1 (17) Stable disease 2 (33) Persistent disease 1 (17) Chemotherapy needed after SVR 3 (50) Abbreviations: IQR, interquartile range; NHL, Non-Hodgkin lymphoma; HCV, hepatitis C virus; DAA, direct acting agents; SVR, sustained virologic response. aNodal (n = 1), Extranodal (n = 2) splenic (n = 1), and mucosa-associated lymphoid tissue lymphomas (n = 2). bFormerly known as interleukin 28b genotype. Disclosures H. Torres, Gilead Sciences: Consultant and Grant Investigator, Consulting fee, Grant recipient and Research support. Merck & Co: Consultant and Grant Investigator, Consulting fee and Grant recipient. Janssen Pharmaceuticals, Inc.: Consultant, Consulting fee. Dynavax Technologies: Consultant, Consulting fee

Background Immune checkpoint inhibitors are a novel class of targeted therapy that activates T cell-mediated tumor cell death. Controversies exist about the safety and efficacy of immunotherapy in patients with chronic viral infections affecting T cells, such as hepatitis C virus (HCV). Herein, we analyzed the effect of immune checkpoint inhibitors on HCV viremia and HCV-related hepatic outcome. Methods HCV-infected patients with solid tumors seen at MD Anderson Cancer Center (November 2012–April 2018) were enrolled in a prospective observational study. Patients were monitored for the development of HCV reactivation (HCV-RNA ≥1 log10IU/mL over baseline), hepatitis flare (alanine transaminase increase to ≥3 times upper limit of normal) and HCV-associated hepatitis (HCV reactivation and hepatitis flare) while on cancer treatment. Results Out of 205 chronically infected patients with solid tumors, 12 (6%) received immunotherapy and were seen in the HCV clinic, but only four (2%) returned for regular monitoring (Table 1). They were followed for 9 months. None of the four patients received concomitant chemotherapy or steroids. Hepatitis flare occurred in three patients, but HCV reactivation or HCV-associated hepatitis was not detected in any study patient. Immune checkpoint inhibitors were discontinued in one patient (25%) due to hepatitis flare unrelated to HCV. Conclusion The use of immune checkpoint inhibitors appears to be safe in solid tumor patients with HCV infection. Table 1. Demographics, Types of Cancer, Immunotherapy Received, and Changes in Serum HCV-RNA Patient Age, years Sex HCV Genotype Cirrhosis Type of Cancer Immunotherapy Baseline HCV-RNA (log 10IU/mL) Highest HCV-RNA After Baseline (log 10IU/mL) Hepatitis Flare 1 67 Male 1a Yes Hepatocellular carcinoma Nivolumab + ipilimumab 5.45 5.08 Yes a 2 52 Male 1a No Melanoma Nivolumab + ipilimumab 6.97 6.95 Yes b 3 57 Male 3 No Melanoma Pembrolizumab 5.72 6.39 No 4 55 Male 1a No Melanoma Ipilimumab 5.75 7.18 c Yes c a After partial hepatectomy. b Negative infectious work-up including hepatitis A, B, E, cytomegalovirus, and herpes simplex virus. c Six months after completing immunotherapy, HCV-associated hepatitis occurred after starting high-dose steroids for brain metastasis. Disclosures H. Torres, Gilead Sciences, Merck & Co., Inc.: Grant Investigator, Grant recipient. Vertex Pharmaceuticals: Grant Investigator, Grant recipient.

Background According to professional societies, the endpoint to consider hepatitis c virus (HCV) infection cured is the achievement of a sustained virologic response 12 weeks after treatment completion (SVR12). Late recurrences (beyond SVR12) are rare. Herein, we report two cases of HCV-infected cancer patients with late relapses post direct-acting antivirals (DAAs). Methods Patients with any type of chronic cancer and HCV treated with DAAs between January 2014 and March 2018 at MD Anderson Cancer Center were prospectively followed. All patients had HCV RNA levels at baseline; 2 and 4 weeks after initiation of DAAs; at end of treatment (EOT); and 12 weeks after completion of DAAs. No phylogenetic analyses were available for samples collected. Results Among 196 HCV-infected cancer patients treated with DAAs, 20 developed viral relapse, 2 (10%) of them with late relapse (Figure 1). Both patients denied behaviors, exposures, and conditions associated with HCV reinfection. Case 1: Fifty-six-year-old male with hepatocellular carcinoma (HCC), HCV genotype 1a, interferon-experienced, with compensated cirrhosis received in 2017 ledipasvir/sofosbuvir for 12 weeks, followed by systemic chemotherapy with sorafenib. He achieved an SVR12 but developed HCV relapse 12 weeks later (24 weeks after EOT). Patient remained infected with HCV 1a. He did not receive retreatment due to HCC not amenable for curative treatment. Case 2: 57-year-old male with multiple myeloma, HCV genotype 1a, interferon-experienced without cirrhosis. He received sofosbuvir and simeprevir in 2015 for 12 weeks. Post DAAs, he received chemotherapy with carfilzomib, lenalidomide, dexamethasone, and ixazomib followed by autologous hematopoietic cell transplant pre-conditioned with melphalan. He achieved both an SVR12 and SVR 24 but had HCV relapse detected during the one year follow-up visit. Patient remained infected with HCV 1a. He has retreated with sofosbuvir, veltapasvir, voxilaprevir and ribavirin and currently with HCV RNA level at EOT. Conclusion Late HCV relapses can occur in HCV-infected cancer patients. Long-term monitoring of HCV-RNA and easy-to-use tests to differentiate relapses from reinfection in real-world practice are warranted in this population. Disclosures H. Torres, Gilead Sciences, Merck & Co., Inc.: Grant Investigator, Grant recipient. Vertex Pharmaceuticals: Grant Investigator, Grant recipient.

Reactivation of chronic hepatitis C virus (HCV) infection has been reported in cancer patients receiving chemotherapy. In this study, we report the first case, to our knowledge, of thalidomide-induced acute exacerbation and reactivation of chronic HCV infection complicating management of multiple myeloma. Sofosbuvir-based antiviral therapy helped achieve viral clearance and normalization of liver enzymes, thus allowing access to future potentially life-saving chemotherapy agents.

Background There is paucity of data regarding IMIs of the CNS in patients with HC or stem cell transplantation (SCT). Methods Review of the records of patients with HC and/or SCT recipients who were diagnosed with CNS IMIs at MD Anderson Cancer Center (1/1/2000–5/31/2016). IMIs were classified as proven or probable (EORTC/MSG criteria). We excluded patients with mixed CNS infections. Risk factors for survival at day 42 post diagnosis (dx) were assessed. A multivariate logistic regression analysis was performed to identify independent predictors of mortality. Results We identified 40 patients (16 proven; 40%). Most patients were white (29; 73%) and male (33; 83%). Median age was 58 years. The most common HC was acute leukemia (23; 58%). Seventeen patients (43%) were SCT recipients; 13 (76%) had GVHD. Most patients had active HC and neutropenia at dx (38; 95% and 21; 53%, respectively). Twenty-seven patients (68%) were in the ICU at dx. Aspergillus sp. (13; 33%) and Mucorales (8; 20%) accounted for >50% of cases. CNS IMIs were deemed to be secondary to direct extension or hematogenous spread in 9 (23%) and 31 (77%) patients, respectively. In the latter group, 28/31 (90%) had fungal pneumonia. Of the 27 and 9 patients who had Aspergillus galactomannan antigen tested from serum and CSF, respectively, 18 had positivity in serum (66%) and 3 in CSF (33%). Most patients (30; 75%) had exposure to mold-active agents within 30d of dx. Most patients (34; 85%) received lipid AMB and were treated with combination therapy (33; 83%). Most CNS lesions presented as ring-enhancing abscesses radiographically (26; 65%). Absence of giant cells and granulomas in the pathologic examination of the brain lesions were associated with increased 42 days mortality (0% vs. 70%, P = 0.01 and 0% vs. 60% in those who survived, P = 0.03, respectively). In multivariate analysis, co-infection at the time of dx was associated with increased mortality (OR: 16.5, 95% CI: 1.4–198.3, P = 0.03) while steroid tapering was associated with decreased mortality (OR: 0.06, 95% CI: 0.01–0.53, P = 0.01). There was a trend towards protective role of surgical drainage (ORn = 0.18, 95% CI = 0.03–1.14, P = 0.07). Conclusion CNS IMIs occur in ill patients with active HC who are often pre-exposed to antifungals. Immune response in pathology, steroid tapering and possibly surgical drainage are associated with improved outcome. Disclosures D. P. Kontoyiannis, Pfizer: Research Contractor, Research support and Speaker honorarium. Astellas: Research Contractor, Research support and Speaker honorarium. Merck: Honorarium, Speaker honorarium. Cidara: Honorarium, Speaker honorarium. Amplyx: Honorarium, Speaker honorarium. F2G: Honorarium, Speaker honorarium

Background Direct-acting antivirals (DAAs) are commonly used in Hepatitis C (HCV)-infected cancer patients. While treatment failure in these patients is rare, little information exists regarding antiviral salvage therapy. We evaluated the treatment outcomes of this patient population. Methods Cancer patients who received initial DAAs (01/2014-06/2016) were analyzed for viral relapse, defined as reappearance of HCV RNA in serum after discontinuation of DAAs. We evaluated safety and efficacy of salvage. RAS (resistance-associated substitutions) to NS5A/B and NS3 were identified using commercially available assays (population sequencing). Results Of 160 patients enrolled in a prospective observational study, 15 (15/160; 9%) experienced treatment failure. Of these, 7 received salvage therapy (7/15; 47%) (Table). The majority of patients were men (86%), cirrhotics (57%), and had solid tumors (71%). Ultimately 3/7 (43%) patients achieved sustained virologic response (SVR). Of the 4 patients who failed first salvage treatment, 3 (75%) had RASs prior to such therapy, 3 (75%) had HCC, and 1 (25%) underwent second salvage. None of the patients experienced grade 3/4 adverse events. Conclusion HCV relapse after DAAs is rare in cancer patients, but the efficacy of salvage is suboptimal. More effective rescue therapies are needed. Disclosures All authors: No reported disclosures. Table: Patient characteristics, DAA regimens, and outcomes Gender Age Genotype Cirrhosis Malignancy IFN experienced DAA regimen failed Duration (weeks) NS3 RAS at failure NS5A/B RAS at failure First salvage DAA Duration (weeks) Adverse Events Grade 3 or 4 Virologic outcome M 56 1a Yes Colon Yes SOF/IFN/RBV 12 No No SOF/LDV 24 No SVR24 M 87 1b Yes HCC No SOF/SIM 12 No No SOF/LDV/RBV 24 No Relapse M 65 1a Yes DLBCL, HCC No SOF/LDV 12 No Q30R SOF/SIM/RBV 24 No Relapse F 56 3a No DLBCL Yes SOF/RBV 24 No No SOF/DCV/RBV 24 No SVR24 M 58 1a No HCC No SOF/LDV 12 No Q30Q/H, Y93H SOF/SIM/RBV 24 No SVR24 M 63 1a Yes HCC Yes SOF/LDV 24 No Q30R SOF/VEL/RBV 24 No Relapse M 66 1a No SCC No SOF/LD 12 Q80K, D168E M38A, Q30H ELB/GZV/RBV 24 No Relapse DCV, daclatasvir; DLBCL, diffuse large B-cell lymphoma; ELB, elbasvir; GZV, grazoprevir; HCC; hepatocellular carcinoma; LDV, ledipasvir; RBV, ribavirin; SCC, squamous cell carcinoma; SIM, simeprevir; SOF, sofosbuvir; SVR24, SVR at 24 weeks.